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Syndromes

Trisomy 21 

Down Syndrome

• Characteristic 

facial features: 

–Upward‐slanting 

palpebral 

fissures 

–Epicanthal folds 

–Flat nasal bridge

Brushfield spots

• Bridged palmar 

crease: two 

transverse palmar 

creases are 

connected by a 

diagonal line 

• Wide space between 

first and second toes 

• Short fifth finger

• Small ears 

• Flat occiput

Trisomy 21: Physical Findings 

• Hypotonia 

• Small head 

• Epicanthal folds 

• Flat nasal bridge 

• Upward slanting 

palpebral fissures 

• Brushfield spots 

• Small mouth and ears 

• Extra skin at the nape 

of neck 

• Single transverse 

palmar crease 

• 5th finger clinodactylyl 

• Sandal toe gap

Trisomy 21: Associated defects 

• Congenital heart defects 

• Mental retardation 

• Leukemia 

• Hearing loss, otitis media 

• Hirschsprung disease, duodenal 

atresia 

• Cataracts 

• Thyroid disease 

• Hip dislocation 

• Atlantoaxial instability/dislocation

Down syndrome 

• 1 in 700 live births 

• >60% spontaneously aborted 

• 20% stillborn 

• Facial appearance permits diagnosis 

• Marked muscle hypotonia as baby 

• Learning difficulty (IQ usually

Three different patterns of chromosomes can cause Down syndrome 

Non‐disjunction 


• 95% people have three separate copies of 

chromosome 21 ‐ trisomy 21 –non disjunction 

•4% have the extra copy of chromosome 

21 because of a Robertsonian translocation 

•1% have mosaicism with normal and 

trisomy 21 cell lines (and usually have much 

milder features because of the presence of 

the normal cells); ‐ occurs postzygotically

Meiotic 


(Trisomy 21: 

75% meiosis 1) 

Trisomy Monosomy (lethal)

Trisomy 21: 47,XX,+21 

three separate copies of chromosome 21

Interphase FISH test for trisomy 21 

The chromosome 21 probe is labelled with a red fluorochrome and a control probe (for 

chromosome 18) is labelled in green. The two green dots show that the hybridization 

has worked for this cell, and the three red dots show that there are three copies of 

chromosome 21. The clinical report is based on examining a large number of cells. For 

prenatal diagnosis a mix of differently coloured probes from chromosomes 13, 18, 21, X 

and Y is often used.

Incidence of trisomy 21 at the time of chorionic villus sampling (10‐11 weeks), amniocentesis (16 weeks) and term. 

The incidence of trisomy 21 increases with increasing maternal age.

Trisomy 21 amniocyte

The trisomy 21 type of Down 

syndrome is the result of an error in 

meiosis, and has a recurrence risk of 

about 1 in 100.

Neonatal features 

• Flat facial profile 

• Poor Moro reflex 

• Excessive skin at the 

nape of neck 

• Slanted palpebral 

fissures 

• Hypotonia 

• Hyper flexibility of 

joints 

• Dysplasia of pelvis 

• Anomalous ears 

• Dysplasia of 

midphalanx of fifth 

finger 

• Transverse palmer 

crease

Mental Retardation 

• Almost all DS babies have MR. 

• Mildly to moderately retarded . 

• Starts in the first year of life. 

• Average age of sitting (11 mon), and walking (26 

mon) is twice the typical age. 

• First words at 18 months. 

• IQ declines through the first 10 years of age, 

reaching a plateau in adolescence that continues 

into adulthood.

Heart Disease 

• 50 % of Down Syndrome pts have heart disease 

• Atrioventricular septal defect 

• VSD / ASD 

• PDA 

• Tetralogy of Fallot 

• Mitral valve prolapse 

• Note: all the anomalies are the common 

malformations observed in the population, none 

of them is observed exclusively in DS

GI abnormalities 

• 5% of cases 

• Duodenal atresia or stenosis, sometimes 

association with annular pancreas in 2.5 % of 

cases 

• Imperforate anus 

• Esophageal atresia with TE fistula is less 

common 

• Hirschsprung’s disease 

• Strong association with celiac disease 5 –16 % , 

5 –16 fold increase as compared to general 

population

Growth 

• BW, length and HC are less in DS 

• Reduced growth rate 

• Prevalence of obesity is greater in DS 

• Weight is less than expected for length in 

infants with DS, and then increases 

disproportionally so that they are obese by 

age 3‐4 yrs

Eye problems 

Most common disorders are 

Refractory error –35 to 76 percent 

Strabismus –25 to 57 percent 

Nystagmus –18 to 22 percent 

Cataract occur in 5 % of newborns. 

Frequency increases with age.

Hematologic disorders 

• The risk of leukemia is 1 to 1.5 percent. 

• 65% of newborn have polycythemia resulting in 

hypoglycemia. 

• Risk of AML and ALL is also much higher than the 

general population. 

• Transient leukemia – exclusively affects NB. 

‐ It is asymptomatic with spontaneous resolution in 2‐ 

3 months. 

‐ Vesiculopustular skin eruptions are common and 

resolve with disorder.

Hearing loss 

• Unilateral or bilateral 

• Conductive, sensorineural or mixed 

• Otitis media is a frequent problem

Endocrine disorder 

• Thyroid disease – Hypothyroidism occurs 

more frequently than hyperthyroidism. 

• Diabetes –The risk of type 1 diabetes is 

three times greater than that of the 

general population.

Mortality 

Median age of death has increased from 25 yrs 

in 1983 to 49 yrs in 1997, an average of 1.7 yrs 

increase per year. 

Most likely cause of death is CHD, Dementia, 

Hypothyroidism and Leukemia. 

Improved survival is because of increased 

placements of infants in homes and 

changes in treatment for common causes of 

death.

REPRODUCTION 

Women with DS are fertile and may 

become pregnant.

REPRODUCTION 

Nearly all males with DS are infertile. 

The mechanism is impairment of 

spermatogenesis

Down’s Syndrome

Analyzing the origin of extra chromosome 21 

? 

p1 p4 

p3 p2

Patau Syndrome 

A picture demonstrating 

polydactyly, or extra fingers, 

a common abnormality in 

Patau syndrome.

Description 

•Patau syndrome ‐ also known as trisomy 13 

and trisomy D. 

•Affects about 1 in 12,000 live births. 

•More than 80% of infants with Patau 

syndrome die within their first year of life. 

The Simian line, or an 

abnormal palm pattern that 

is usually a symptom of 

Patau syndrome. 

Cayden Phipps: 3A ‐ Abrams 36

History 

Patau syndrome, or “Trisomy 13”, as it was first 

called, was first observed by Thomas Bartholin in 

1657. However, the actual genetic and 

chromosomal‐related parts of it were discovered 

by Dr. Klaus Patau in 1960, hence the name 

“Patau syndrome”. 


Trisomy 13

Common Problems cont. 

Muscular and skin problems: 

• Polydactyly, or extra fingers/toes 

• Low‐down ears 

• Prominent heels and deformed feet, called ‘rocker‐bottom’ feet 

• Strange palm patterns, commonly called the Simian line 

• Overlapping of the fingers over thumb 

• Cleft palate 

Polydactyly The Simian line ‘Rocker-bottom’ feet 


Common Problems, cont. 

Vascular Problems: 

• Kidney problems 

• Heart defects such as ventricular septal defect 

Kidney Problem 

The disease shown 

right is called 

Polycystic kidney 

disease (PKD). 

This is a disorder in 

which clumps of cysts 

develop within your 

kidneys. Cysts are 

small round sacs 

containing water-like 

fluid. 


Common Problems 

Nervous system problems: 

• Mental and motor disabilities 

• Microcephaly, or a less rounded brain resulting in more of an 

egg‐shaped skull 

• Eye structure defects: 

• Microphthalmia, or crossed eyes (may involve one eye or both) 

• Cataracts 

• Sensory Nystagmus, or involuntart “twitching” of the eye 

• Optic nerve hypoplasia, or the underdevelopment of the optic 

nerve 

S 


Treatment 

• There is no treatment to address the condition. 

However, there are procedures to sustain life for a 

bit. 

• Most times, surgery is required to fix defects to 

allow the child to survive for as long as possible. 

• Most infants with Patau syndrome die within the 

first year of life, but many children have trouble 

surviving the first few days or weeks of life due to 

severe neurologic and vascular problems. 

43

Mosaic Patau 

A small percentage of cases occur when only 

some of the body’s cells have an extra copy of 

chromosome 13, resulting in a mixed population 

of cells with differing numbers of chromosomes. 

This is called Mosaic Patau. 

A baby with a cleft palate, a 

common abnormality of Patau 

syndrome. 

Cayden Phipps: 3A ‐ Abrams 

44

Edwards Syndrome- 

Trisomy 18 

is a rare genetic disorder 

caused by an extra copy of 

chromosome18.

Trisomy 18 (Edward) 

• Incidence 1:4000 live births 

• Males : females 1:3 

• 5‐10% survive first year 

• Death usually due to heart failure or 

pneumonia

• L 

• O 

• L 

• S S 

• C 

• U 

• F 

• G 

• S 

• H

•Meckel’s diverticulum, horseshoe 

kidneys 

• Dorsiflexed short hallux 

•Short sternum, mental retardation

• Prominent occiput and low‐set, posteriorly 

rotated malformed auricles 

• Clenched hand showing typical pattern of 

overlapping fingers 

• Rocker‐bottom feet

Imprinting: Definition and historical 

perspectives 

• Imprinting: an epigenetic modification to 

DNA that results in “memory of parental 

origin” 

• By convention, the inactive allele is said to 

be “imprinted” 

• Early evidence: 

– early embryo nuclear transfer experiments 

– gynogenetic and androgenetic embryos fail to 

survive

Imprinting: Mechanisms and purpose 

• Epigenetic modification that is 

reversible in germ line 

• DNA methylation and chromatin 

configuration are important 

• Imprinting may be a reflection of 

“parental conflict:” 

– paternal gene for rapid growth 

– maternal genes for growth retardation to 

maximize litter size

Experimental and clinical evidence for 

imprinting 

• Mouse embryology ‐ opposite phenotypes 

in cases of uniparental disomy 

• Human imprinting syndromes: 

– Prader‐Willi syndrome (inheritance of paternal 

deletion ‐‐‐> maternal monosomy) 

– Angelman syndrome (inheritance of maternal 

deletion ‐‐‐> paternal monosomy) 

– Beckwith‐Wiedemann syndrome ‐ paternal 

disomy

Map of Imprinted 

Regions in Human 

Genome 

Maternally inherited 

homolog (left) 

Paternally inherited 

homolog (right)

Genomic Imprinting

Angelman 

• Seizures 

• Jerky, ataxic movements 

• Abnormal facies 

• Chromosome 15 deletion with maternal 

imprinting

• Maxillary hypoplasia 

• Large mouth 

• Prognathism

• Low tone 

• Large appetite— 

obesity 

• Hypogonadism 

• Developmental 

delay/MR 

• Chromosome 15 

deletion, paternal 

imprinting 

Prader‐Willi

• Marked obesity 

• Excess fat over the 

trunk, buttocks, and 

proximal extremities 

• Small hands (and 

feet) 

• Hypoplastic penis and 

scrotum

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